Humans ; Cyclin D1 ; Melanoma ; Skin Neoplasms ; Cyclin-Dependent Kinase 4

OBJECTIVE: The objective of this study was to evaluate the relationship between the expression of cyclin B1, D1 and the various prognostic factors in ovarian carcinoma. METHODS: In this study, fresh ovarian tissue samples were obtained from 41 patients treated surgically at our institute from March of 2002 to February of 2005. These included 36 ovarian carcinomas and 5 normal ovarian tissues that were served as the control. Quantitative real-time RT-PCR and Western blot analysis were used in detecting the expression of mRNA and protein of cyclin B1, D1, respectively. RESULTS: The mean 2(-delta delta CT) values of cyclin B1 and D1 mRNA in ovarian carcinoma tissues obtained through quantitative real-time RT-PCR were 5.83+/-12.03, 17.60+/-22.20, respectively, and the mean values in the control were 0.55+/-0.35, 0.50+/-0.26, respectively. The results showed difference in the expression, but were not statistically significant (p=0.67, 0.07, respectively). If the mean densitometer value of cyclin B1 and D1 protein in the control obtained by Western blot analysis was 1, the mean values in ovarian carcinoma tissues were higher, but were not statistically significant (1.30+/-0.73, 1.81+/-1.28, respectively) (p=0.76, 0.06, respectively). The expression of cyclin B1, D1 and various prognostic factors was not statistically related. CONCLUSION: Our results showed that the expression of cyclin B1 and D1 in ovarian carcinoma tissues was higher than in the normal control. This suggested that cyclin B1, D1 and the tumorigenesis and the degree of malignancy was closely related. But the expression of cyclin B1, D1 and various prognostic factors was not statistically related. Further studies based on the correlation between cyclin and response to treatment or survival rate are needed to support cyclin as a prognostic factor of ovarian carcinoma.
Blotting, Western ; Carcinogenesis ; Cyclin A ; Cyclin B1* ; Cyclin D1 ; Cyclins* ; Humans ; RNA, Messenger ; Survival Rate

BACKGROUND/AIMS: Gastric carcinoma is a major cause of morbidity and mortality in Korea. It evolves through dysplasia to an invasive adenocarcinoma. The carcinogenesis of dysplasia and adenocarcinoma in the stomach was investigated by examining the levels of mutant p53 protein, p21(waf1/cip1), and cyclin D1 expression in gastric dysplasia and invasive adenocarcinoma. METHODS: Formalin- fixed paraffin-embedded tumors were examined immunohistochemically using the monoclonal antibodies to the 53 protein, p21(waf1/cip1) and cyclin D1. RESULTS: Mutant p53 protein, p21(waf1/cip1) and cyclin D1 expression were found in 66.6% (12/18), 72.2% (13/18) and 33.8% (6/18) of dysplasia, and 45.0% (9/20), 15.0% (3/20) and 30.0% (6/20) of invasive adenocarcinoma, respectively. CONCLUSIONS: These results suggest that p21(waf1/cip1), which is controlled by the p53 protein, plays a more important role in the carcinogenesis of the stomach than cyclin D1.
Adenocarcinoma* ; Antibodies, Monoclonal ; Carcinogenesis ; Cyclin D1* ; Cyclins* ; Korea ; Mortality ; Stomach*

BACKGROUND: Aberrations of cell cycle-related genes have been reported to contribute to the formation and development of various human tumors. To investigate the gastric carcinogenesis, the expression of cell cycle-related genes (p53, p21wafl/cipl, cyclin D1 and Rb protein) compared to the morphological changes of gastric epithelial lesions were studied. METHODS: The expression of p53, p21wafl/cipl, cyclin D1 and Rb protein was immunohistochemically studied in a series of surgical specimens including the 36 normal/regenerating lesions and the 127 gastric epithelial proliferative lesions (GEPLs). The gastric epithelial proliferative lesions consisted of 25 regenerating epithelia with atypias (REAs), 27 low grade gastric dysplasias (LGDs), 17 high grade dysplasias (HGDs), 24 early gastrc carcinomas (EGCs), and 34 advanced gastric carcinomas (AGCs). RESULTS:The frequency of p53 protein overexpression was significantly associated with histologic grades of GEPLs (p=0.031); occurring in 4% of REAs, in 14.8% of LGDs, in 23.5% of HGDs, in 41.7% of EGCs and 58.9% of AGCs. The p21 wafl/cipl immunohistochemical reaction showed superficial eccentric positivity, representing an inverse correlation with histologic grades of GEPLs (p=0.04); occurring in 83.4% of normal/regenerating lesions, in 80% of REAs, in 74.1% of LGDs, in 29.4% of HGDs, 20.8% of EGCs and 8.8% of AGCs. Although Cyclin D1 and Rb proteins were expressed highly in the GEPLs, the frequency of both proteins were insignificantly associated with histologic grades of GEPLs (p=0.092). However, cases with both the Rb and cyclin D1 positivity were increased with statistical significance along histologic grades of GEPLs (p=0.044). CONCLUSIONS: The altered expression of p53, p21, Rb, and cyclin D1 was considered to be related to dysplastic progression and advancement of malignancy in GEPLs. Therefore, immunohistochemical studies of cell cycle related proteins and a combined analysis may be useful for estimating and following up cases of GEPLs.
Carcinogenesis ; Cell Cycle ; Cyclin D1* ; Cyclins* ; Humans ; Retinoblastoma Protein

No abstract available.
Breast Neoplasms* ; Breast* ; Cyclin D1* ; Cyclins* ; Survival Rate*

BACKGROUND AND OBJECTIVES: The p16, cyclin D1, their partners Cdk4/Cdk6, and pRb constitute a G1 regulatory pathway commomly targeted in tumorigenesis. Genetical, immunochemical, and functional analyses show abnormalities of this pathway in various tumors including head and neck squmaous cell carcinoma. To investigate the clinicopathologic meanings of p16 protein and the relationship between p16 and cyclin D1 in head and neck squmous cell carcinoma. MATERIAL AND METHOD: Formalin-fixed paraffin-embeded tumor materials that were obtained from 37 patient with head and neck squmaous cell carcinoma were analyzed by immunohistochemical staining method using antiserum that were directed against p16 and cyclin D1. RESULTS: 1) Deletion of p16 was found in 67.6% (25/37) of the patients with head and neck squamous cell carcinoma. The deletion was not associated with the clinicopathologic parameters (eg. T and N stages, cell differentiation). 2) Deletion of p16 protein and overexpression of cyclin D1 were identified in 76% (28/37) of the patients with head and neck squmaous cell carcinoma. But deletion of p16 was not affected by the overexpression of cyclin D1 in head and neck squmaous cell carcinoma. CONCLUSION: Deletion of p16 and overexpression of cyclin D1 were identified in head and neck squmaous cell carcinoma. These may abrogate the G1 regulatory pathway. These data suggested that combination of these abnormalities may be important in head and neck turmorigenesis.
Carcinogenesis ; Carcinoma, Squamous Cell* ; Cyclin D1* ; Cyclins* ; Head* ; Humans ; Neck*

BACKGROUND: Inactivation of the retinoblastoma protein (pRb) is a mechanism by which tumor cells can subdue normal growth control. Among the molecules involved in control of pRb phosphorylation, cyclin D1 and cyclin E have been found to be deregulated and overexpressed in various types of cancers. METHODS: Immunohistochemical stains for pRb, p16, cyclin D1 and cyclin E were performed in 73 cases of infiltrating duct carcinomas of the breast. In addition to analysis of their expression rates, the relationships between their expressions and the clinicopathologic parameters were evaluated. RESULTS: pRb, p16, cyclin D1 and cyclin E were positive in 64.7% (44 out of 68 cases), 24.6% (15 out of 61 cases), 43.8% (32 out of 73 cases) and 61.6% (45 out of 73 cases), respectively. Their expression rates were not significantly associated with clinicopathologic prognostic factors. 33 out of 38 cases with p16-negative reactions were pRb positive, while 10 out of 15 cases with pRb-negative reactions were p16 positive. There was a significant inverse relationship between pRb and p16 expressions (P<0.005). 25 out of 32 cases with cyclin E-positive reactions were cyclin D1-positive, and 25 out of 45 cases with cyclin D1-positive reactions were cyclin E-positive. A statistically significant association was observed between cyclin D1 and cyclin E expressions (P<0.05). CONCLUSIONS: The main mechanism during tumorigenesis of breast carcinoma depends on the cyclin D1/p16/pRb pathway, but cyclin E might play a role in the absence of cyclin D1. The inverse correlation between the pRb and p16 expressions may represent one of the important mechanisms in tumorigenesis, as well.
Breast Neoplasms ; Breast* ; Carcinogenesis ; Coloring Agents ; Cyclin D1* ; Cyclin E* ; Cyclins* ; Phosphorylation ; Retinoblastoma ; Retinoblastoma Protein

PURPOSE: To evaluate the clinical impact of the altered expression of cell cycle regulators in stage I and II breast cancers. MATERIALS AND METHODS: The interaction between cyclin D1/E and p27Kip1 expressions were analyzed using tissue microarray (TMA) technology in 133 breast cancers. Data from the immunohistochemical assays of 3 molecules were merged, and analyzed, with a Ki67 labeling index of the same tumors. RESULTS: Cyclin D1 was expressed in 72 breast carcinomas (54.1%) and cyclin E in 60 (45.1%) out of the 133 breast carcinomas. Expressions of cyclin D1 and cyclin E were inversely related to each other, and significantly associated with the estrogen receptor (ER) expression and differentiation of the breast carcinoma. The expression of cyclin E was significantly decreased in tumors expressing cyclin D1 (p=0.022). There was a trend for cyclin D1 expression to increase in tumors expressing p27Kip1 (p=0.053), but the expression of cyclin E did not correlate with p27Kip1 expression. The Ki67 labeling index was markedly increased in tumors expressing cyclin E, whereas it was significantly decreased in the cyclin D1 or p27Kip1 expressing-tumors. From survival analysis, cyclin E expression was the only significant variable for the prediction of poor survival. CONCLUSION: The abnormal expressions of cell cycle regulatory molecules are prevalent, and interrelated with each other in breast cancer. Integration of TMA technology allowed a high-throughput analysis for correlating molecular the in situ findings, with the clinico-pathologic information. Among the three molecules studied, the cyclin E had a prognostic implication for stage I and II breast cancer.
Breast Neoplasms* ; Breast* ; Cell Cycle ; Cyclin D1* ; Cyclin E* ; Cyclins* ; Estrogens ; Prognosis

OBJECTIVETo investigate the expression of five kinds of cyclins in hepatocellular carcinoma (HCC) and their association with degree of tumor differentiation, metastasis and infection of hepatitis B virus (HBV).

METHODSThe HCC tissue microarrays were composed of those from 273 cases of HCC tissues, 144 surrounding-tumor liver tissues and 10 normal liver tissues obtained from autopsy. The diameter of each specimens on tissue microarrays was 2.0 mm. Immunohistochemistry was used to detect the expression of cyclin A, cyclin B, cyclin D1, cyclin D3 and cyclin E on HCC tissue microarrays. The association of the expression of these cyclins with the infection rate of HBV was also analyzed.

RESULTSThree paraffin-embedded HCC tissue microarrays were successfully constructed, including 136, 143 and 148 tissue spots, respectively. The positive rates of cyclins in 273 cases of HCC were cyclin A 52.7%, cyclin B 45.4%, cyclin D1 35.9%, cyclin D3 44.3% and cyclin E 23.1%; while the figures in 144 surrounding-tumor tissues were 8.3%, 5.6%, 4.9%, 6.3% and 1.4%, respectively. In 10 normal liver tissues these cyclins exhibited negative staining, with the exception that cyclin D1 was positive in one case of normal liver tissue. The positive rate of cyclins in HCC were significant higher than those in surrounding-tumor liver tissues (P < 0.01), in HCC tissues with histological grade II and III, the cyclins expression were stronger than that in grade I (P < 0.05). The positive rates of cyclins, except cyclin A in HCC with portal vein invasion were higher than those without portal vein invasion (P < 0.01). Infection of HBV did not have significant relationship with the expression of cyclins (P > 0.05).

CONCLUSIONCyclins in different cell cycles overexpressed at varied levels in hepatocellular carcinoma, and the increased expression of cyclins may shorten the tumor cell cycle phase, accelerate cell proliferation, and have a close relationship with HCC aggressiveness.

Carcinoma, Hepatocellular ; chemistry ; Cyclin A ; analysis ; Cyclin B ; analysis ; Cyclin D1 ; analysis ; Cyclin D3 ; Cyclin E ; analysis ; Cyclins ; analysis ; Hepatitis B ; metabolism ; Humans ; Immunohistochemistry ; Liver Neoplasms ; chemistry

OBJECTIVETo investigate the expression of human telomerase reverse transcripase (hTERT), cyclin D1 mRNA, p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein in human ameloblastoma (ABs).

METHODSThe expression of hTERT, cyclin D1, p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein in 54 cases of human ABs were detected by in situ hybridization or immunohistochemistry.

RESULTSThe positive cases of hTERT mRNA, cyclin D1 mRNA was 51, 23, respectively. The positive cases of p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein was 17, 12, 9. Comparing with recurred and transformed malignantly, the expression of hTERT mRNA, cyclin D1 mRNA increased, and the expression of p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein decreased or lost. The expression of hTERT mRNA and pl6(INK4), p21(WAF1) mRNA and p27(KIP1) protein in ABs had middle to high negative relation (r(k) = -0.587, r(k) = -0.652, r(k) = -0.783, P < 0.001).

CONCLUSIONThe hTERT mRNA expression in ABs is related to the reguation of pl6(INK4), p21(WAF1) mRNA and p27(KIP1) protein.

Ameloblastoma ; Cyclin D1 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclins ; Humans ; Immunohistochemistry ; RNA, Messenger ; Telomerase